The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease

Prenzler, Shane; Rudrawar, Santosh; Waespy, Mario; Kelm, Sørge; Anoopkumar‐Dukie, Shailendra; Haselhorst, Thomas

doi:10.1080/08830185.2021.1931171

Cited by 16 publications

(13 citation statements)

References 185 publications

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“…The desorption efficiency of PEG on mPEG 2000 CHS-modified LNPs or mPEG 2000 DMG-modified LNPs was measured in mouse serum at 37 °C, following the research method of Xu et al [ 25 ]. The results showed that mPEG 2000 CHS could be cleaved by 60 % after being incubated with mouse serum at 37 °C for 12 h. However, the mPEG 2000 DMG could dissociate from the LNPs by only 16 %.…”

Section: Resultsmentioning

confidence: 99%

“…We examined the transfection efficiency of various mRNA LNPs in dendritic cells (DCs) and macrophages, as these two types of cells are the main antigen-presenting cells (APCs) and abundantly express Siglec-1 [ [24] , [25] , [26] ]. DC2.4 cells and RAW264.7 cells were selected as the in vitro dendritic cell and macrophage models, respectively, for the expression of Siglec-1 on the surface of these cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles

Tang,

Zhang,

Sui

et al. 2024

Materials Today Bio

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles

Tang,

Zhang,

Sui

et al. 2024

Materials Today Bio

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“…Additionally, expression of IL2RA, which can be induced by TNF signaling and is upregulated under chronic inflammatory conditions [ 27 ], was dose-dependently reduced in the sera of patients receiving povorcitinib. Finally, expression of LTA, a protein associated with chronic wounds [ 28 ]; SIGLEC1, an IFN-responsive protein restricted to monocytes and macrophages that suppresses antiviral innate immune response [ 29 , 30 ]; TNC, an extracellular matrix glycoprotein elevated in several inflammatory diseases [ 31 , 32 , 33 ]; and CLEC7A (or dectin-1), a protein involved in innate immune responses [ 34 ], were also all dose-dependently reduced. Together, these data corroborate findings from the clinical efficacy of povorcitinib as demonstrated in the phase 2 studies that showed a dose-dependent clinical improvement, with the proteomic analysis suggesting a rapid effect on protein expression [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Disease-Associated Pathways in Hidradenitis Suppurativa by the Janus Kinase 1 Inhibitor Povorcitinib: Transcriptomic and Proteomic Analyses of Two Phase 2 Studies

Liu

Santos

Smith

2023

IJMS

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Janus kinase (JAK)/signal transducer and activator of transcription signaling (STAT) has been implicated in the pathophysiology of hidradenitis suppurativa (HS). This study evaluated treatment-related transcriptomic and proteomic changes in patients with moderate-to-severe HS treated with the investigational oral JAK1-selective inhibitor povorcitinib (INCB054707) in two phase 2 trials. Lesional skin punch biopsies (baseline and Week 8) were taken from active HS lesions of patients receiving povorcitinib (15 or 30 mg) once daily (QD) or a placebo. RNA-seq and gene set enrichment analyses were used to evaluate the effects of povorcitinib on differential gene expression among previously reported gene signatures from HS and wounded skin. The number of differentially expressed genes was the greatest in the 30 mg povorcitinib QD dose group, consistent with the published efficacy results. Notably, the genes impacted reflected JAK/STAT signaling transcripts downstream of TNF-α signaling, or those regulated by TGF-β. Proteomic analyses were conducted on blood samples obtained at baseline and Weeks 4 and 8 from patients receiving povorcitinib (15, 30, 60, or 90 mg) QD or placebo. Povorcitinib was associated with transcriptomic downregulation of multiple HS and inflammatory signaling markers as well as the reversal of gene expression previously associated with HS lesional and wounded skin. Povorcitinib also demonstrated dose-dependent modulation of several proteins implicated in HS pathophysiology, with changes observed by Week 4. The reversal of HS lesional gene signatures and rapid, dose-dependent protein regulation highlight the potential of JAK1 inhibition to modulate underlying disease pathology in HS.

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“…Rather than a direct measurement of type I interferons its influence on immune cells is accessed by interferon-induced transcripts (IFITs) in whole blood or PBMCs ( 35 ). Other surrogate parameters of type I interferon signature such as CD169 or STAT1 have been used ( 36 , 37 ). Others have shown that impaired INF-type I response might lead to increased virus replication and dysregulated pulmonary inflammation.…”

Section: Discussionmentioning

confidence: 99%

Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19

et al. 2022

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ObjectivesTo determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP).MethodsPatients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models.ResultsThe majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models.ConclusionThis analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.

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The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease

Cited by 16 publications

References 185 publications

Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles

Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles

Modulation of Disease-Associated Pathways in Hidradenitis Suppurativa by the Janus Kinase 1 Inhibitor Povorcitinib: Transcriptomic and Proteomic Analyses of Two Phase 2 Studies

Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19

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